Vision loss or blindness in many human retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, is a result of the degeneration of photoreceptor cells. At present, there is no real treatment or cure for the blind. Most of the current approaches that are attempting to develop treatments for the blinding disorders are based on two strategies: one involves transplantation of normal or stem cells into the diseased retinas and the other provides electrical-stimulation via retinal implants. We propose a new strategy that aims to restore a certain level of vision for the blind suffering from photoreceptor degeneration. Our strategy is to enable the remaining second or third order neurons in photoreceptor degenerative retinas to respond to light by expressing light-gated channels in their membranes. This strategy is likely to be feasible both mechanistically and technically and can avoid many obstacles encountered by the current approaches. Particularly, directly light-gated micro-type rhodopsins, channelrhodipsins, have been recently cloned and functionally expressed in mammalian cell lines. Studies in blind patients and in animal models suggest that the second and third order retinal neurons remain, in part, preserved in the diseased retinas. Furthermore, it is possible that exogenous genes can be introduced into retinal neurons by means of gene therapy. The objective of this proposal is to conduct feasibility studies for this strategy in rodent models. The specific hypotheses that we will test in this proposal are: 1) directly light-gated channelrhodopsins can be functionally expressed in mammalian retinal neurons, 2) the remaining retinal second and third order neurons in the photoreceptor-degenerative retinas retain their physiological capacity to relay and process visual signals. These studies will establish a foundation for further work leading to the development of a potentially effective treatment for the blinding disorders as well as techniques with valuable applicability in biomedical research. [unreadable] [unreadable] [unreadable]